Dear colleague,

Italian Association Against Arthritis, AICA, born in 1992, is a non profit association whose main aims are to provide informations concerning the treatment of arthritides and to update on rheumatic diseases.

The Association is pleased to announce the conclusion of the preliminary research carried out by Dr. Caruso et al, leading to the development of a promising therapeutic vaccine for rheumatoid arthritis.

The researches on immunotherapy for rheumatoid arthritis (RA) started in 1976 at L. Sacco Hospital (Milan), where it was observed, for the first time, that Rifamycin SV, an old antibiotic endowed with cytolitic properties, injected by intra-articular route, developed significant therapeutic effects in arthritides, The systemic effects obtained when the application of intra-synovial treatment with Rifamycin SV was extended to many joints, have led us to hypothesize that this antibiotic, once infiltrated in joints, frees the pathogenic peptide from synovial cells which interact with the antigen-binding site on the membrane of an anti-idiotype T-cell (paratope) activating an immunoregulatory response.The idiotype-anti-idiotype network on membrane is considered central in immunoregulation involving autoantigens. This mechanism could provide an endogenous, antigen-specific, autonomic immunotherapy.

We have recently reported that the ultrafiltrate of longstanding rheumatoid synovial fluid and the ultrafiltrate of autologous PBMC lysates, subcutaneously administered, are effective in treating rheumatoid arthritis; the former being much more effective than the latter.

The thread that links the two treatment approaches is the pivotal role of the unknown pathogenic peptides that are released from RA synovial cells, following the treatment with Rifamycin SV, and those that are thrown out from disrupted mononuclear cells (freezing/thawing) during the preparation of ultrafiltrates, which are then subcutaneously injected.

Our strategy to extract and identify the pathogenic epitopes was linked to the notion that in a systemic disease such as RA, the arthritogenic epitope would be present in all antigen-presenting cells, including circulating cells, as well as in synovial cells.

Here, these bioactive peptides are spontaneously released from endosomal compartment and gradually accumulate in synovial fluid as a consequences of the lysis of proliferating synoviocites and deeper mononuclear cells in inflamed synovium. In synovial fluid the pathogenic epitopes would be in a free state and can be ultrafiltered directly since they can pass through an ultrafilter with a cut off of 10kDa

Once subcutaneously injected in RA patients, the bioactive peptides contained in the ultrafiltrates are transported by dendritic cells in inflammatory sites where they can induce the expansion of the regulatory T cell populations, thereby exerting suppressive action. The peptide would not interact with autoreactive T lymphocytes, since they are not associated with class II MHC molecules, and thus would bypass the most detrimental component of the immune response in patients with arthritis.

Soon, an article by dr. Innocenzo Caruso concerning the oldest and most fascinating enigma of RA and the associated conditions such as pregnancy and hepatocellular jaundice, will be posted in the site of AICA. The amelioration in pregnant women and the flare at delivery could be due the freed epitopes which can trigger two different effector mechanisms: one, as mentioned above, is potentially protective; the other, consisting of the self-epitope-receptor microcomplexes, that are spontaneously formed throughout the course of RA, could elicit immune-inflammatory responses. Soon, the results of these studies will be available in this site from which they can be downloaded. Further on, a hypothetical method for the separation and identification of the autoantigens of rheumatoid arthritis will be posted.

Kindest regards.

Innocenzo Caruso, email corresponding author
Past-chief of rheumatology unit of L. Sacco hospital, Milan, Italy
Honorary president of AICA